酵母RNA聚合酶Ⅱ羧基端结构域激酶CTDK-Ⅰ及其亚基的结构与功能

Structure and function of yeast RNA polymerase Ⅱ carboxyl-terminal repeat domain kinase CTDK-I and its subunits

RNA聚合酶Ⅱ最大亚基Rpb1的羧基端结构域(carboxyl-terminal repeat domain,CTD)是RNA聚合酶Ⅱ发挥转录延伸功能所必需的,对其执行精确的转录调节功能至关重要。酵母细胞周期蛋白依赖性激酶CTDK-Ⅰ (carboxyl-terminal repeat domain kinase,CTDK-Ⅰ)由CTK1、CTK2和CTK3组成,作用于RNA聚合酶Ⅱ羧基端结构域,动态磷酸化CTD的七肽重复序列(YSPTSPS)来调控转录和翻译。酵母中的特异性蛋白CTK3与特殊的细胞周期蛋白CTK2结合形成异二聚体,再与CTDK-Ⅰ的催化亚基CTK1结合以调节其活性。CTK1作为细胞周期蛋白CDK (cyclin dependent kinase,CDK)的同源蛋白,其结构与功能的研究可拓展人们对CDK蛋白家族的认识;CTK2-CTK3复合物对CTK1调控机制的研究也可为细胞周期蛋白抑制剂的研发提供新的思路。本文简述了酵母CTDK-Ⅰ的功能特点及其亚基的结构与功能以及亚基间的相互作用,并展望了CTDK-Ⅰ复合物的研究前景。

Carboxyl-terminal repeat domain（CTD） of RNA polymerase Ⅱ largest subunit Rpb1 is essential for transcription regulation. Carboxyl-terminal repeat domain kinase（CTDK-Ⅰ） is composed of CTK1, CTK2 and CTK3, acting on RNA polymerase Ⅱ carboxyl-terminal repeat domain and phosphorylating CTD heptapeptide repeat（YSPTSPS） for regulating transcription and translation. The specific protein CTK3 binds to cyclin CTK2 to form a heterodimer, controlling CTK1 activity by binding to CTK1. Structural and functional study of CTK1, a homologous protein of cyclin dependent kinase（CDK）, may provide a new idea for the research of CDK family, and analysis of the regulatory mechanism of activation of CTK1 by CTK2-CTK3 complex may offer an innovative method for developing cell cycle protein inhibitors. This article reviews the functional characteristics of CTDK-Ⅰ and the structures and interactions of its subunits and provides a useful guide for the studies of CTDK-Ⅰ complex in the future.